Fibrinogen and Fragments

Domain Structure of Fibrinogen
The trinodular arrangement of the Aα, Bβ, and γ chains, the IIa cleavage sites (IIa) releasing FPA and FPB, as well as the plasmin cleavage sites (Pm) yielding Fragment D and Fragment E are shown.

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The thrombin (IIa) catalyzed cleavage of soluble fibrinogen (Fbg) to form fibrin (Fbn) is the terminal proteolytic event in the coagulation cascade. These soluble Fbn monomers spontaneously polymerize to form an insoluble Fbn network which is stabilized by the factor XIIIa catalyzed crosslinking of lys and glu residues of α and γ chains. This Fbn network is the major protein component of the hemostatic plug.

Plasma fibrinogen is large glycoprotein (Mr=340,000) synthesized in the liver and circulating at a concentration of 2.6 mg/ml. It is a disulfide linked dimer composed of 3 pairs of disulfide linked non-identical polypeptide chains (Aα, Bβ and γ). Notable features of the Aα chain are the N-terminal peptide (fibrinopeptide A (FPA, 1-16)), factor XIIIa crosslinking sites and 2 phosphorylation sites. When synthesized, Fbg is fully phosphorylated, but circulates at only 20-30% phosphorylation. The Bβ chain contains fibrinopeptide B (FPB, 1-14), one of the 3 N-linked carbohydrate moieties (Mr=2500) and an N-terminal pyroglutamic acid. The γ chain contains the other N-linked glycosylation site and a factor XIIIa crosslinking sites. The 2 elongated subunits ((AαBβγ)2) are aligned in an antiparallel manner forming a trinodular arrangement of the six chains. The nodes are formed by disulfide rings between the 3 parallel chains. The central node (n-disulfide knot, E domain) is formed by the N-termini of all six chains held together by 11 disulfide bonds. This region contains the 2 IIa-sensitive sites. The release of FPA by cleavage at R16-G17 generates Fbn I, exposing a polymerization site (17-20) on the Aα chain. These regions bind to complimentary regions on the D domain of Fbn to form protofibrils. Subsequent IIa cleavage of FPB (R14-G15) from the Bβ chain exposes additional polymerization sites and promotes lateral growth of the Fbn network.

Each of the 2 domains between the central node (E domain) and the C-terminal nodes (D domain) is composed of parallel α-helical regions of the Aα, Bβ and γ chains coiled around each other to form a “coiled coil” with polar residues directed outward and nonpolar residues forming a hydrophobic core. In this region, all 3 chains possess a protease (plasmin) sensitive site. The other major plasmin sensitive site is in the hydrophilic preturbance of the α-chain from the C-terminal node. Controlled plasmin degradation at these sites converts Fbg into fragment D and fragment E. The individual fragments are isolated by salt fractionation, gel filtration and ion exchange chromatography. The fragments are supplied lyophilized for storage at 4°C. Highly purified research grade fibrinogen (>95% clottable) is prepared by a combination of conventional and affinity techniques. It is supplied as a frozen solution in ctirate-phosphate for storage at -80°C.

Sample gel image
GelNovex 4-12% Bis-Tris
Load1 µg per lane; purified human fibrinogen
StandardSeeBluePlus 2; Myosin (191 kDa), Phosphorylase B (97 kDa), BSA (64 kDa), Glutamic Dehydrogenase (51 kDa), Alcohol Dehydrogenase (39 kDa), Carbonic Anhydrase (28 kDa), Myoglobin Red (19 kDa), Lysozyme (14 kDa)
LocalizationPlasma, platelets
Plasma concentration2.6 mg/ml
Mode of actionPrecursor molecule which is cleaved by thrombin to form fibrin clot.
Molecular weight340,000
Extinction coefficient
1 %
1 c m, 280 nm
= 15.1
Isoelectric point5.1-6.3
StructureDimer of 3 pairs of non-identical chains Aα (Mr= 66,800), Bβ (Mr= 52,000) and γ (Mr=46,500), Elongated trinodular molecule with 2 terminal D domains and one central E domain. Factor XIIIa cross-linking sites at E328, E366, K508, K584 in Aα chain; at E398 and K406 in Bβ chain.
Percent carbohydrate3%
Post-translational modificationsAα chain: 2 phosphorylated serines, S3, S346
Bβ chain: N364 glycosylation site Mr= 2500, N-terminal pyroglutamic acid
γ chain: glycosylated N52
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  5. Doolittle, R.F., J.Mol.Biol., 120, 311-325 (1978).
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  9. Furlan, M., in Human Protein Data, Fibrinogen, Haeberli,A., ed., VCH Publishers, N.Y. (1995).
  1. Akhter, S., et al., Proc Natl Acad Sci U S A. 2002 July 9; 99(14): 9172–9177. (Fibrinogen polymerization)
  2. Lu, C., et al., Arthritis Rheum. 2005 December ; 52(12): 4018–4027. (Detection of tPA antibodies)

This publication list is not all encompassing, and is only meant to provide limited examples of how Prolytix products are used. We encourage you to search the literature for other examples pertinent to your experimentation, and to contact us with any technical questions.

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